Dementia prevalence is expected to triple worldwide over the next 40 years at tremendous monetary and emotional cost. My research is designed to minimize the impact of the impending dementia epidemic using a three-pronged approach: 1) identifying risk factors for cognitive impairment and dementia in older adults; 2) developing dementia prediction models that can be used to estimate the impact of risk factor reduction and to target prevention strategies toward those who are at greatest risk; and 3) development and evaluation of interventions to delay onset or slow progression of cognitive impairment and dementia.

Much of my early research focused on performing observational studies to identify factors associated with increased or decreased risk of cognitive decline and dementia. I was particularly interested in the potential protective effects of physical activity, and a major contribution of my work has been the use of objective measures (rather than self-report) to assess physical activity levels in observational studies. In one study, we found that elders with higher levels of cardiorespiratory fitness ? as measured objectively using peak oxygen consumption during exercise treadmill testing ? experienced less cognitive decline over a 6-year follow-up period (Barnes et al, J Am Geriatr Soc 2003). In a second study, we found that older women who moved more during the day ? as measured objectively using wrist actigraphy ? had higher levels of cognitive function and a lower risk of cognitive impairment (Barnes et al., J Am Geriatr Soc 2008). I also am interested in the potential beneficial effects of mental activity on cognitive function in older adults and published an early study demonstrating a strong relationship between literacy and cognitive function (Barnes et al., J Gerontol Med Sci 2004). Our work also has found that depressive symptoms are associated with an increased risk of mild cognitive impairment (Barnes et al., Arch Gen Psychiatry 2006), and I received funding from NARSAD to build on this work by studying the effects of depression over the life course on late-life risk of dementia (Barnes et al., Arch Gen Psychiatry 2012). In addition, we have found that older women who experience long-term maintenance of cognitive function are less likely to have diabetes, hypertension or difficulty with daily activities and more likely to have healthy behaviors and good social networks (Barnes et al., J Am Geriatr Soc 2007) and that older adults who have both high secondhand smoke exposure and carotid artery stenosis are at particularly high risk of dementia (Barnes et al., Am J Epidemiol 2010). In Veterans, we have found that traumatic brain injury (Barnes et al., Neurology 2014) and prisoner of war (POW) status (Meziab et al., Alzheimers Dement 2014) are independent risk factors for dementia. Together, these studies suggest that there are a variety of potential strategies for lowering risk of cognitive impairment and dementia in late life.

Another major focus of my work has been on development of dementia risk indices that can be used to identify elders with a high dementia risk in different settings as well as risk prediction models to project the potential impact of changes in risk factor profiles. As successful strategies for enhancing cognitive function and preventing dementia are developed, it will be critically important to be able to identify high-risk elders to target for intervention. My first publication in this area (Barnes et al., Neurology 2009) found that a combination of demographic, cognitive, behavioral, functional, medical, genetic, cerebral MRI findings and carotid artery ultrasound measures could be used to predict an individual?s six-year risk of dementia with high accuracy. This publication generated substantial interest from clinicians and researchers world-wide as well as the lay press, including interviews with CBS Evening News, ABC News Online, US News & World Report, and Time. I subsequently was invited to write an editorial about the future role of dementia risk indices (Barnes & Yaffe, Future Neurology 2009) and to present on the risk index approach at the invitation-only Leon Thal Symposium ?09. In a follow-up publication, I found that an abbreviated index that included only items that could be administered quickly without special equipment was almost as accurate as the original index (Barnes et al., Alzheimer?s & Dementia 2010). This line of research led to my involvement with an NIA workgroup that developed a simple Dementia Screening Indicator tool for primary care settings to help identify high-risk elders who should be considered for cognitive screening as part of the new Annual Medicare Wellness Visit, and I was selected to be lead author of the writing group (Barnes et al, Alzheimers Dementia 2014). I also have developed a prediction model to identify older adults with mild cognitive impairment who have an increased risk of progressing to Alzheimer's disease (Barnes et al., Alzheimer's & Dementia 2014). Furthermore, I expanded on this work by projecting the potential impact of risk factor reduction on future dementia prevalence (Barnes and Yaffe, Lancet Neurology 2011; Norton et al, Lancet Neurology 2014). We found that 30-50% of Alzheimer's disease cases are potentially attributable to 7 modifiable risk factors--including physical inactivity, low education, smoking, depression, diabetes, mid-life hypertension and mid-life obesity--and that relatively small reductions in these risk factors at a societal level could potentially prevent millions of cases of Alzheimer's disease from ever occurring. These findings also received extensive international media coverage, including the New York Times, Wall Street Journal, and International Herald Tribune. Several recent studies have supported these projections by showing that age-adjusted dementia prevalence rates are declining in many countries in parallel with changes in societal-level risk factors such as improved education, reduced smoking and better control of vascular risk factors.

My most recent research is focusing on performing randomized, controlled trials (RCTs) to evaluate the effectiveness of interventions for enhancing cognitive and physical function in late life. I participated in a pilot RCT of a computer-based cognitive training program in individuals with mild cognitive impairment (Barnes et al., Alz Disease Assoc Disord 2009). In addition, I designed and implemented a larger RCT comparing the effects of different physical (aerobic vs. stretching) and mental (intensive computer training vs. educational DVDs) activities on cognitive function in older adults who self-reported a recent decline in memory or thinking (Barnes et al., JAMA Intern Med 2013; Pa et al., JAGS 2015; Poelke et al, Int Psychogeriatr 2016; Kalapatapu J Addict Dis 2017). This trial, called the Mental Activity and eXercise (MAX) Trial, was funded jointly through funds from my K01 award and an Alzheimer?'s Association grant. In addition, I have recently led the development of a novel integrative exercise program for people with dementia call Preventing Loss of Independence through Exercise (PLIÉ) that incorporates training of procedural memory for basic daily movements with mindful body awareness and social connection through group movement. Our pilot study results suggested that PLIÉ is associated with meaningful improvements in cognitive function, physical function, quality of life and caregiver burden, with effect sizes that are two to three times larger than current dementia medications (Barnes et al., PLoS One 2014; Wu et al., Aging Ment Health 2014). I am PI of a VA Merit grant to study the efficacy of PLIÉ in a full-scale RCT and an Alzheimer's Association grant to test an adapted version for pairs of affected individuals and care partners (Paired PLIÉ). In addition, I received a VA Innovators award to begin to spread the program to other sites. I am deeply committed to performing research that is designed to help older adults maintain cognitive function, physical function and quality of life.